ArticleThe Biochemical journal2007
Autophosphorylation-dependent degradation of Pak1, triggered by the Rho-family GTPase, Chp.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Review
- RHOV Is a Detachment-Responsive Rho GTPase Necessary for Ovarian Cancer Peritoneal Metastasis.Cancer research · 2026Article
- Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms.Nature communications · 2024Article
- Atypical RhoUV GTPases in development and disease.Biochemical Society transactions · 2024Review
- Molecular basis and current insights of atypical Rho small GTPase in cancer.Molecular biology reports · 2024Review
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- Molecular Pathways Involved in the Anti-Cancer Activity of Flavonols: A Focus on Myricetin and Kaempferol.International journal of molecular sciences · 2022Review
- Group I PAKs in myelin formation and repair of the central nervous system: what, when, and how.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Derivation of stationary distributions of biochemical reaction networks via structure transformation.Communications biology · 2021Article
- Regulation and functions of RhoU and RhoV.Small GTPases · 2020Review
- Review
- Ubiquitination and Long Non-coding RNAs Regulate Actin Cytoskeleton Regulators in Cancer Progression.International journal of molecular sciences · 2019Review
- p-21 Activated Kinase as a Molecular Target for Chemoprevention in Diabetes.Geriatrics (Basel, Switzerland) · 2018Review
- Atypical RhoV and RhoU GTPases control development of the neural crest.Small GTPases · 2015Review
- The C. elegans Chp/Wrch Ortholog CHW-1 Contributes to LIN-18/Ryk and LIN-17/Frizzled Signaling in Cell Polarity.PloS one · 2015Article
- Rho GTPases: masters of cell migration.Small GTPases · 2014Review
- JosD1, a membrane-targeted deubiquitinating enzyme, is activated by ubiquitination and regulates membrane dynamics, cell motility, and endocytosis.The Journal of biological chemistry · 2013Article
- Phosphorylation of histone H3 on Ser10 by auto-phosphorylated PAK1 is not essential for chromatin condensation and meiotic progression in porcine oocytes.Journal of animal science and biotechnology · 2013Article
- Analysis of Rho GTPase expression in T-ALL identifies RhoU as a target for Notch involved in T-ALL cell migration.Oncogene · 2013Article
- LAT-independent Erk activation via Bam32-PLC-γ1-Pak1 complexes: GTPase-independent Pak1 activation.Molecular cell · 2012Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Paks (p21-activated kinases) Pak1, Pak2 and Pak3 are among the most studied effectors of the Rho-family GTPases, Rac, Cdc42 (cell division cycle 42) and Chp (Cdc42 homologous protein). Pak kinases influence a variety of cellular functions, but the process of Pak down-regulation, following activation, is poorly understood. In the present study, we describe for the first time a negative-inhibitory loop generated by the small Rho-GTPases Cdc42 and Chp, resulting in Pak1 inhibition. Upon overexpression of Chp, we unexpectedly observed a T-cell migration phenotype consistent with Paks inhibition. In line with this observation, overexpression of either Chp or Cdc42 caused a marked reduction in the level of Pak1 protein in a number of different cell lines. Chp-induced degradation was accompanied by ubiquitination of Pak1, and was dependent on the proteasome. The susceptibility of Pak1 to Chp-induced degradation depended on its p21-binding domain, kinase activity and a number of Pak1 autophosphorylation sites, whereas the PIX- (Pak-interacting exchange factor) and Nck-binding sites were not required. Together, these results implicate Chp-induced kinase autophosphorylation in the degradation of Pak1. The N-terminal domain of Chp was found to be required for Chp-induced degradation, although not for Pak1 activation, suggesting that Chp provides a second function, distinct from kinase activation, to trigger Pak degradation. Collectively, our results demonstrate a novel mechanism of signal termination mediated by the Rho-family GTPases Chp and Cdc42, which results in ubiquitin-mediated degradation of one of their direct effectors, Pak1.
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